Quantum chemical studies of the reaction mechanisms of enzymatic CO2 conversion.

Enzymatic capture and conversion of carbon dioxide (CO2) into value-added chemicals are of great interest in the field of biocatalysis and have a positive impact on climate change. The quantum chemical methods, recognized as valuable tools for studying reaction mechanisms, have been widely employed in investigating the reaction mechanisms of the enzymes involved in CO2 utilization. In this perspective, we review the mechanistic studies of representative enzymes that are either currently used or have the potential for converting CO2, utilizing the quantum chemical cluster approach and the quantum mechanical/molecular mechanical (QM/MM) method. We begin by summarizing current trends in enzymatic CO2 conversion, followed by a brief description of the computational details of quantum chemical methods. Then, a series of representative examples of the computational modeling of biocatalytic CO2 conversion are presented, including the reduction of CO2 to C1 species (carbon monoxide and formate), and the fixation of CO2 to form aliphatic and aromatic carboxylic acids. The microscopic views of reaction mechanisms obtained from these studies are helpful in guiding the rational design of current enzymes and the discovery of novel enzymes with enhanced performance in converting CO2. Additionally, they provide key information for the de novo design of new-to-nature enzymes. To conclude, we present a perspective on the potential combination of machine learning with quantum description in the study of enzymatic conversion of CO2.

Excessive dietary soluble arabinoxylan impairs the intestinal physical and immunological barriers via activating MAPK/NF-κB signaling pathway in rainbow trout (Oncorhynchus mykiss).

Arabinoxylan (AX) has been deemed as an antinutritional factor, but limited information has addressed the effects of dietary AX on intestinal health of fish. The present study investigated the effects of dietary AX on intestinal mucosal physical and immunological barriers of rainbow trout (Oncorhynchus mykiss). Five isoproteic and isolipidic experimental diets (AXE, AX0, AX2.5, AX5 and AX10) were formulated to contain 0.03% arabinoxylanase as well as 0%, 2.5%, 5% and 10% AX, respectively. Each diet was randomly distributed to triplicate groups of 35 juvenile (average weight 3.14 ± 0.02 g) per tank in a rearing system maintained at 17 ± 1 °C for 9 weeks. Dietary AX supplementation regardless of inclusion levels significantly (P < 0.05) depressed the growth performance and feed utilization. The plasma endothelin-1 and d-lactic acid contents as well as diamino oxidase activity were significantly higher in fish fed diet AX10 compared to fish fed diet AX0. Dietary inclusion of 5-10% AX resulted in decreased intestinal villus height, goblet cell number and desmosome density, increased crypt depth, short and irregular microvilli, widened intercellular space; down-regulated the mRNA levels of occludin in hindgut, claudin3 and ZO-1 in foregut and midgut, but up-regulated the mRNA levels of claudin12 and claudin15 in midgut as well as claudin23 in foregut, midgut and hindgut. Furthermore, dietary 5-10% AX supplementation decreased the midgut and hindgut complement 3, complement 4 and sIgT contents as well as the midgut IgM and hindgut IL-10 contents. Conversely, the hindgut TNF-α and IL-6 contents increased with the rising dietary AX level. RT-qPCR demonstrated that the pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-12ß, IFN-γ, and TNF-α) and pIgR mRNA levels in midgut and hindgut were up-regulated by dietary AX inclusion of 5-10% AX. Meanwhile, the mRNA levels of p38 MAPK, IκBα, and NF-κB p65 in midgut and hindgut raised gradually with the increasing dietary AX content. The Western blot results showed that the protein expression levels of p38 MAPK and NF-κB generally increased with the rising dietary AX content. Dietary treatment with 0.03% arabinoxylanase did not affect the growth performance and intestinal health of rainbow trout (P > 0.05). In conclusion, excessive dietary AX inclusion (5-10%) increased the intestinal permeability and induced the intestinal inflammatory response via activating MAPK/NF-κB signaling pathway, and ultimately damaged the intestinal barrier function of rainbow trout.

Utilization of PAX1 methylation test for cervical cancer screening of non-HPV16/18 high-risk HPV infection in women.

Aim: To evaluate the clinical performance of PAX1 methylation (PAX1m) and cytology for patients with non-HPV16/18 high-risk HPV (hrHPV) infection. Methods: Cervical exfoliated cells from 387 outpatients with non-HPV16/18 hrHPV - positive were collected for cytology and PAX1m assays. Results: The PAX1m level increased with the severity of cytology and histopathology. For cervical intraepithelial neoplasia (CIN)CIN2+/CIN3+, the areas under the curve were both 0.87. The specificity and positive predictive value (PPV) of PAX1m were greater than abnormal cytology (CIN2+ specificity: 75.5 vs 24.8%; PPV: 38.8 vs 18.7%; CIN3+ specificity: 69.3 vs 22.7%; PPV: 14.0 vs 6.7%). Conclusion: PAX1m increased specificity and PPV for CIN2+/CIN3+ compared with cytology for women with non-HPV16/18 hrHPV (+).

The hepatoprotective effect of Sophora viciifolia fruit extract against acetaminophen-induced liver injury in mice.

This research demonstrated the protective effect and possible mechanism of the Sophora viciifolia extract (SVE) against acetaminophen-induced liver injury in mice. The levels of ALT and AST in the serum and antioxidant enzyme activity in the liver were measured. We used immunohistochemistry to detect CYP2E1, Nrf2, and Keap1 protein expression in the liver. The mRNA expression in the liver of TNF-α, NF-κB, and IL-6, Nrf2 and its downstream genes HO-1 and GCLC were measured by qRT-PCR. We found that SVE could decrease the ALT and AST levels, promote the activities of SOD, CAT, GSH-Px, and GSH, and ameliorate pathological liver lesions. SVE could down-regulate the mRNA expression of inflammatory factors and up-regulate Nrf2, HO-1 and GCLC. SVE reduced the protein expression of the CYP2E1 and increased the Nrf2 and Keap1. SVE has been shown to have a protective effect against APAP-induced liver injury, possibly through activation of the Keap1-Nrf2 pathway.

Development and validation of the Health Education Adherence Scale for Stroke Patients: a cross-sectional study.

BACKGROUND: Due to the lack of health education adherence assessment tools for stroke patients, the assessment of health education adherence in this population is insufficient, which hinders the prevention and rehabilitation of stroke. This study aims to develop and validate a Health Education Adherence Scale for Stroke Patients (HEAS-SP). METHODS: A cross-sectional design with a purposive sampling method was used for this study. Six hundred and fifty-four eligible participants completed the demographic questionnaire and the HEAS-SP. The data collection lasted for 7 months, from March 1stto September 30th in 2019. Item analysis and exploratory and confirmatory factor analysis were employed to develop and validate the HEAS-SP. RESULTS: The item analysis, exploratory and confirmatory factor analysis resulted in a 20-item HEAS-SP with 4 domains: medication adherence, diet adherence, rehabilitation exercise adherence, and healthy lifestyle adherence. The four-domain model demonstrated acceptable model fit indexes and the 20-item HEAS-SP demonstrated acceptable reliability and validity. CONCLUSION: The 20-item HEAS-SP was shown to have acceptable reliability and validity for assessing health education adherence with respect to diet, medication, rehabilitation exercise and healthy lifestyle in stroke patients, making it a potential basis for developing targeted interventions for stroke patients.

A predictive nomogram for a failed trial of labor after cesarean: A retrospective cohort study.

AIM: To validate risk factors and a nomogram prediction model for the failure of a trial of labor after cesarean section (TOLAC) in a Chinese population. METHODS: We included women who tried TOLAC between January 2017 and May 2019, grouped according to the success/failure of TOLAC. The patients were randomized 3:1 into the development and validation sets. Multivariable logistic regression analyses were used to develop a nomogram prediction model for TOLAC failure. RESULTS: In total, 535 (86.3%) of the women (n = 620) aged 29-34 years had a successful vaginal birth after cesarean (VBAC). All women had a fully healed previous uterine incision. The univariable analyses showed that the cephalopelvic score (p < 0.001), BMI (p = 0.001), full engagement into the pelvis (p < 0.001), Bishop cervical maturity score (p < 0.001), and estimated fetal weight at admission (p < 0.001) could enter the multivariable model. Furthermore, the multivariable analysis showed that the cephalopelvic score (OR = 0.42, 95%CI: 0.23-0.77, p = 0.005), full engagement in the pelvis (OR = 0.16, 95%CI: 0.08-0.33, p < 0.001), and Bishop cervical maturity score (OR = 0.46, 95%CI: 0.35-0.59, p < 0.001) were independent predictors of the failure of TOLAC. CONCLUSION: This study proposes a nomogram that can assess the risk of failure of TOLAC in Chinese pregnant women. The statistical model could help clinicians know the likelihood of successful TOLAC in the clinical setting.

LncRNA TDRG1 promotes the proliferation, migration, and invasion of cervical cancer cells by sponging miR-214-5p to target SOX4.

The pathogenesis of cervical cancer (CC) at molecular level has attracted much research attention. The current study aimed to explore the effects of LncRNA TDRG1 on cellular process in CC cells and its molecular mechanism. Expressions of TDRG1 and miR-214-5p in CC and normal tissues and CC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of TDRG1, miR-214-5p, and SOX4 on cell proliferation, migration, invasion, and EMT process of CC cells were detected by Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, Transwell, and Western blot assays, respectively. StarBase and Targetscan7.2 were used to predict the target genes of TDRG1 and miR-214-5p, and the predictions were verified by dual-luciferase reporter assay. The expression of SOX4 in CC and normal tissues, and CC cells transfected with siTDRG1 or miR-214-5p inhibitor was determined by qRT-PCR. The results showed that expression of TDRG1 was up-regulated, while that of miR-214-5p was down-regulated in CC. The target genes of TDRG1 and miR-214-5p were verified to be miR-214-5p and SOX4, respectively. Knocking down TDRG1 expression could inhibit cell proliferation, colony, migration, and invasion abilities, and EMT process, whereas the inhibition of miR-214-5p expression partially reversed such results. Moreover, high SOX4 expression was observed in CC tissues, and down-regulating TDRG1 expression reduced the SOX4 expression while down-regulating miR-214-5p expression alleviated such an inhibition. In conclusion, TDRG1 acts as cancer promoter in CC through promoting cell proliferation, migration, invasion, and EMT process to modulate SOX4 expression through adsorbing miR-214-5p.

Application of quality control circle in the treatment of moderate cancer pain in inpatients.

CONTEXT: Pain is one of the most common and intolerable symptoms in cancer patients. But cancer pain control is still negative in China. OBJECTIVES: This paper explores the application of quality control circle in the treatment of cancer pain in inpatients to improve the quality of life of patients with cancer pain. METHOD: Established a quality control circle group to analyze the current status of cancer pain control in inpatients with moderate cancer pain, set goals, formulate corresponding countermeasures and implement and review them in stages. The plan-do-check-act method was cyclically applied. The Brief Pain Inventory was used to evaluate the cancer pain status of patients with cancer pain hospitalized before (January to April 2016) and after (September to December 2016) the implementation of quality control circle activities. RESULTS: The pain control effect of the observation group was significantly better than that of the control group. The mean (standard deviation) of pain severity and pain interference in the observation group were significantly lower than those in the control group (6.21 [2.86] vs 4.31 [2.25], 10.54 [4.10] vs 7.25 [3.77]). There was significant difference after the implementation of quality control circle (P < 0.01). CONCLUSION: Quality control circle activities are used to manage patients with cancer pain, to improve the situation of pain control and to improve the quality of life of patients. This management tool and method is worthy of clinical promotion and application.

Phytochemicals Content, Antioxidant and Antibacterial Activities of Sophora viciifolia.

The objective of this study is to compare the efficacy of ethanol extracts from different parts of Sophora viciifolia. The content of polyphenols, flavonoids, alkaloids, and antioxidant capacity, antimicrobial activity were investigated, and individual polyphenols and alkaloids were analyzed and quantified by ultra-high performance liquid chromatography (UPLC). The microdilution method was used to determine the antimicrobial activity of extracts from S. viciifolia on six strains. The results for extracts from the different parts (flowers, leaves, and fruit) were compared in varying concentrations to determine whether one extract source is superior to another. Testing verified that extracts from the different parts of S. viciifolia did vary, as expected. For example, extract from the leaves had the best antimicrobial activity against pathogenic Candida albicans, but all extracts had good antimicrobial activity against the six tested strains. These results reveal that the active substances in S. viciifolia are abundant and have good antioxidant and antimicrobial activities, which can provide theoretical support for the subsequent development and utilization of S. viciifolia extracts.

Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways.

Vitiligo is a depigmentation disorder characterized by loss of functional melanocytes of the skin epidermis. The pathogenesis of vitiligo remains elusive. The purpose of this study is to investigate the effects of basic fibroblast growth factor (bFGF) on melanocyte migration, including its biochemical mechanism using transwell assay in vitro. We found that melanocyte treated with bFGF showed a significant increase in migration and cytoskeletal rearrangement. These changes were associated with increased activation of PI3K/Akt, Rac1, FAK, JNK, and ERK. Likewise, reduction of PI3K/Akt, Rac1, FAK, JNK, and ERK activity using selective inhibitors or siRNA was associated with impediment of bFGF-induced melanocyte migration. In addition, activity of Rac1, FAK, and JNK was reduced in cells in which PI3K/Akt was inhibited, activity of FAK and JNK was reduced in cells in which the Rac1 was inhibited, and activity of JNK was reduced in cells in which the FAK was inhibited. Collectively, these data demonstrate that bFGF facilitated melanocyte migration via PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways. © 2016 IUBMB Life, 68(9):735-747, 2016.

Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, resulting in a huge medical burden worldwide. Accumulating evidence suggests that the gut microbiome and bile acids play pivotal roles during the development of NAFLD. Patients with NAFLD exhibit unique signatures of the intestinal microbiome marked by the priority of Gram-negative bacteria, decreased ratio of Firmicutes/Bacteroidetes (F/B), and increased Prevotella and Lachnospiraceae. The intestinal microbiota is involved in the metabolism of bile acids. Ursodeoxycholic acid (UDCA) is a key determinant in maintaining the dynamic communication between the host and gut microbiota. It generally shows surprising therapeutic potential in NAFLD with several mechanisms, such as improving cellular autophagy, apoptosis, and mitochondrial functions. This action is based on its direct or indirect effect, targeting the farnesoid X receptor (FXR) and various other nuclear receptors. This review aims to discuss the current studies on the involvement of the microbiome-UDCA interface in NAFLD therapy and provide prospective insights into future preventative and therapeutic approaches for NAFLD.

Protective effects of chlorogenic acid against cyclophosphamide induced liver injury in mice.

We investigated possible protective effects of chlorogenic acid (CGA) against cyclophosphamide (CP) induced hepatic injury in mice. We measured aminotransferase alanine transaminase (ALT) and aspartate transaminase (AST) levels in the serum. We assayed catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hepatic tissue. We assessed expression of nuclear transcription factor 2 (Nrf2) and Kelch sample related protein-1 (keap1) proteins in hepatic tissues using immunohistochemistry. The relative mRNA expression levels of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Hematoxylin & eosin staining was used to assess liver histopathology. We found that administration of CGA prior to induction of injury by CP decreased serum ALT, AST and MDA expressions in hepatic tissue, while CAT, SOD, GSH and GSH-Px concentrations were increased. We found that hepatocytes of animals administered CGA gradually returned to normal morphology. CGA increased the protein expression of Nrf2 in murine hepatic tissue. Administration of CGA up-regulated mRNA expression levels of HO-1, NQO1, TNF-α and IL-6 in hepatic tissue. CGA exhibited a marked protective effect on CP induced liver injury in mice.

Efficacy of probiotic supplementation and impact on fecal microbiota in patients with inflammatory bowel disease: a systematic review and meta-analysis of randomized controlled trials.

Context: Research regarding the treatment of inflammatory bowel disease (IBD) with probiotics has not yielded consistent results. OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy of probiotics supplementation in patients with IBD. DATA SOURCES: Randomized controlled trials (RCTs) evaluating the efficacy of probiotics in patients with IBD were searched in PubMed, the Google Scholar database, Web of Science, and CrossRef for the period July 2003 to June 2023. DATA EXTRACTION: The RCTs were extracted, independently by 2 authors, according to the PICOS criteria. DATA ANALYSIS: Seven studies, including a total of 795 patients, met the study criteria. Five end points were selected to evaluate the efficacy. Of these, 3 indicators showed a statistically significant difference in efficacy: C-reactive protein (odds ratio [OR]: -2.45, 95% confidence interval [CI]: -3.16, -1.73, P < .01), the number of fecal Bifidobacterium (OR: 3.37, 95% CI: 3.28, 3.47, P < .01), and Lactobacillus(OR: 2.00, 95% CI: 1.91, 2.09, P < .01). The other 2 indicators (disease activity for Crohn's disease and for ulcerative colitis) showed no statistically significant difference, while the OR reflected a positive correlation. CONCLUSION: Probiotics supplementation may have a positive effect on IBD by reducing clinical symptoms, reducing the serological inflammatory markers, and increasing favorable gut flora in patients with IBD. Additional RCTs are needed to evaluate the therapeutic effect of probiotics in IBD.

Transatmospheric ileal stoma manometry can be applied for the early detection of stoma outlet obstruction.

Background: Stoma outlet obstruction (SOO) is a common complication of diverting ileostomy and usually detected at the advanced stage when the intestine is obviously obstructed. The objective of this study is to explore the efficacy of transatmospheric ileal stoma manometry (TISM) in early detection of SOO before the manifestation of intestinal obstruction. Methods: A single-center prospective study was performed in patients scheduled to undergo reversal ileostomy and laparoscopic anterior rectal resection and diverting ileostomy in Second Affiliated Hospital of Zhejiang University School of Medicine from 1st July 2022 to 31st December 2022. The stoma pressure was measured by TISM at different time points. Results: The mean stoma pressure of the 30 patients before reversal ileostomy was 5.21 cmH2O which was considered as normal standard of stoma pressure, and ranged from 1.2 to 8.56 cmH2O. After excluding two patients with anastomotic leakage, a total of 38 patients who were subjected to laparoscopic anterior rectal resection and diverting ileostomy were further included in this study. The incidence of anastomotic leakage was 5% and that of SOO was 12.5%. The mean postoperative obstruction time was 5.2 (3-7) days and the mean time from elevated stoma pressure to diagnosed as SOO was 2.8 (2-4) days in the five patients who developed SOO. The pressure measured at the third stoma manometry time point (second day after return of gut function) (10.23 vs. 6.04 cmH2O, p<0.001) and the postoperative hospital stay (10 vs. 8.49 days, p=0.028) showed significantly difference between the SOO and non-SOO groups. The pressures measured at the first time point (before return of gut function) (4 vs. 4.49 cmH2O, p=0.585), the second time point (the day of return of gut function) (6.8 vs. 5.62 cmH2O, p=0.123), and the fourth time point (discharge day) (5.88 vs. 5.9 cmH2O, p=0.933) showed no significant difference in both groups. Conclusion: TISM can be utilized for early detection of SOO and can be incorporated as a novel diagnostic method together with abdominal CT scan to realize the goal of ERAS.

Nerve Growth Factor Protects Retinal Ganglion Cells Related to Inhibiting Endoplasmic Reticulum Stress by Inhibiting IRE1-JNK-CHOP Signaling Pathway.

BACKGROUND: Under various physiological conditions, endoplasmic reticulum stress can induce apoptotic cell death, leading to brain and retinal neuronal cell death, but the relations of ER stress-induced apoptosis and the nerve growth factor's therapeutic effect in Glaucoma optic neuropathy still unclear. METHODS: An endoplasmic reticulum stress model was established in ganglion cells using TG, the endoplasmic reticulum stress inducer. MTT assay and flow cytometry were used to detect the protective effect of NGF on retinal ganglion cells. Western blot was used to detect apoptosis-related proteins Bcl-2, Bad and endoplasmic reticulum stress-related proteins GRP78, IRE1, JNK and CHOP. RESULTS: MTT assay and flow cytometry showed NGF can protect the apoptosis of ganglion cells. Western blot analysis showed the level of pro-apoptotic protein Bad was decreased and anti-apoptotic protein Bcl-2 was increased after NGF treatment. Endoplasmic reticulum stress-induced proteins GRP78, IRE1, JNK and CHOP are counter- acted by NGF. CONCLUSION: NGF protects retinal ganglion cells related to inhibiting endoplasmic reticulum stress by inhibiting IRE1-JNK-CHOP signaling pathway.

Mediating Role of Resourcefulness in the Relationship Between Illness Uncertainty and Poststroke Depression.

Objectives: To examine the association between illness uncertainty, resourcefulness, and poststroke depression (PSD) and identifies whether stroke patients' resourcefulness plays a mediating role in the relationship between illness uncertainty and PSD. Methods: A cross-sectional study was conducted from September 2020 to April 2021. A convenience sample of 355 stroke patients was recruited. A general characteristic questionnaire, the Mishel Uncertainty in Illness Scale, the Resourcefulness Scale (RS), and the Patient Health Questionnaire-9 (PHQ-9) were used to obtain data. Descriptive analysis, Student's t-test, Mann-Whitney U-test, chi-squared test, hierarchical regression analyses, Pearson correlation analysis, and mediation analysis with the PROCESS macro were used to analyze the data. Results: Illness uncertainty, resourcefulness, and PSD were significantly related to each other. Resourcefulness partially mediated the relationship between illness uncertainty and PSD. Conclusion: Illness uncertainty and resourcefulness were significantly associated with PSD, and resourcefulness played a mediating role between illness uncertainty and PSD. Interventions designed to reduce illness uncertainty and enhance resourcefulness may contribute to the prevention and improvement of PSD.

Diagnosis and treatment of uterine artery pseudoaneurysm: Case series and literature review.

BACKGROUND: Uterine artery pseudoaneurysm (UAP) is a rare but potentially life-threatening cause of hemorrhage. Nonetheless, its knowledge could be insufficient among obstetricians, gynecologists, and radiologists. We aimed to clarify the clinical characteristics, management, and outcomes of UAP. METHODS: We retrospectively analyzed nine female patients diagnosed with UAP at our institute between 2013 and 2020. RESULTS: Seven cases presented with a history of traumatic surgery including cesarean section, dilation and curettage, laparoscopic myomectomy, and cervical conization. Two cases occurred after spontaneous vaginal delivery and second-trimester pregnancy termination. The main symptom was heavy/massive/prolonged vaginal bleeding. All patients were first evaluated by color Doppler ultrasonography and three cases were confirmed by magnetic resonance imaging. Severn patients underwent transarterial embolization (TAE) of the uterine arteries, and two were managed conservatively. All patients had good outcomes. CONCLUSIONS: UAP can develop after traumatic pelvic operations and non-traumatic delivery/abortion. It may be more common than previously considered. The risk of rupture may be correlated with multiple factors other than the mass size. TAE of the uterine artery could be an effective management strategy for ruptured UAP. However, some cases can resolve spontaneously without TAE, suggesting that conservative management can be employed in some women.

Photodynamic Treatment of Colorectal Cancer Using Chlorin e6-Loaded Poly(lactide-co-glycolide)- Based Nanoparticles.

We prepared poly(lactide-co-glycolide) (PLGA) encapsulated with chlorin e6 (Ce6) in an effort to increase the stability and efficiency of photosensitizers for photodynamic therapy (PDT). We determined that Ce6-loaded PLGA nanoparticles (PLGA-Ce6 NPs) had drug-loading efficiency of 5%. The efficiency of encapsulation was 82%, the zeta potential was- 25 mV, and the average diameter was 130 nm. The encapsulation of Ce6 in PLGA nanoparticles showed excellent stability. The nanoparticles exhibited sustained Ce6 release profiles with 50% released at the end of 3 days, whereas free Ce6 showed rapid release within 1 day. Ce6 release patterns were controlled by encapsulation into PLGA. The uptake of PLGA-Ce6 NPs was significantly enhanced by endocytosis in the first 8 hours in the HCT-116 cell line. An intracellular reactive oxygen species assay revealed the enhanced uptake of the nanoparticles. An in vitro anti-tumor activity assay showed that the PLGA-Ce6 NPs exhibited enhanced phototoxicity toward HCT-116 cells and a slightly lower IC50 value in HCT-116 cells than Ce6 solution alone. Exposure of HCT-116 cell spheroids to PLGA-Ce6 NPs penetrated more profoundly and had better phototoxicity than pure drugs. These findings suggest that PLGA-Ce6 NPs might serve as PDT for colorectal cancer.

Nasopharyngeal metastasis from colorectal cancer: a case report.

Metastases from colorectal cancer can occur either through the lymphatic or by hematogenous spread. The most common metastatic sites are the lung and liver. Nasopharyngeal metastasis from colorectal cancer has never been previously reported in the literature on the internet databases we can found. In this paper, we present the case of a 79-year-old male suffering from adenocarcinoma of the rectum with distant metastases to the liver, lung, and nasopharynx. Over the previous 7 years, he had received treatment for rectal cancer including radical surgery (miles surgery), chemotherapy, hepatectomy, and pneumonectomy. After local nasopharyngeal radiotherapy, the patient's quality of life significantly declined and they eventually died of dyspnea caused by airway obstruction due to a nasopharyngeal mass after 7 months of palliative treatment involving pain relief from end-stage disease. Nasopharyngeal metastases from colorectal cancer are extremely rare in the clinic. To the best of our knowledge, this is the first case reporting this occurrence which not only extends the disease database but also warns doctors to pay more attention to these clinical scenarios. Strict monitoring of patients with colorectal cancer after primary treatment could lead to the early diagnosis of metastases and give patients better opportunities for treatment and improved prognosis.

Antioxidant Effects of Sophora davidi (Franch.) Skeels on d-Galactose-Induced Aging Model in Mice via Activating the SIRT1/p53 Pathway.

This study investigated the protective effect of Sophora davidi (Franch.) Skeels fruits extract (SDE) on d-galactose-induced acute aging in mice. Ultra performance liquid chromatography coupled with tine-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to identify the composition of compounds in SDE. KM mice were divided stochastically into the normal control group (NC, saline), d-galactose (D-gal) model group, vitamin C (Vc) group (positive control), low-, medium-and high-dose SDE treat groups. After 28 days administration and fasting overnight, the serum, liver, and brain samples of mice were collected. The levels of inducible nitric oxide synthase (iNOS), acetylcholinesterase (AChE) activity in the brain, malondialdehyde (MDA) and reduced glutathione (GSH) content, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activity in the liver and brain were measured. Immunohistochemistry was applied to detect silent information regulator 1 (SIRT1) and p53 protein expression in the liver and brain, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of nuclear factor κB (NF-κB), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and anti-aging factor Klotho in the liver and brain. The results showed that UPLC-Q-TOF/MS identified 78 compounds in SDE. SDE could reduce the iNOS activity in serum and AChE activity in the brain, upregulate the levels of SOD, T-AOC and GSH in liver and brain, and debase the MDA content in liver and brain. SDE could downregulate the mRNA expressions of TNF-α, NF-kB, IL-1ß, and IL-6 in the liver and brain, and elevate the mRNA expression of Klotho. SDE improved the pathological changes of the liver and brain induced by D-gal, increased the expression of SIRT1 protein in the liver and brain, and inhibited the expression of p53 protein induced by D-gal. To summarize, SDE demonstrated clear anti-aging effect, and its mechanism may be relevant to the activation of the SIRT1/p53 signal pathway.